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Framework programme: 6
Call: 1
Project number:
EC contribution: € 15,250,000
Duration: 60 months
Type: IP
Starting date: 1 December 2003
Graphic element Mucosal Vaccines for Poverty Related Diseases
Keywords: Mucosal vaccines; Mycobacterium tuberculosis; tuberculosis; HIV; AIDS


Human Immunodeficiency Virus and Mycobacterium tuberculosis enter the human body at mucosal sites. The aim of the present project is to develop mucosally delivered vaccines against HIV and TB, which will induce local immunity able to neutralise the pathogens at their port of entry and systemic immunity able to prevent systemic spread of the infection. The possible development of mucosal vaccines against malaria will be also investigated. The goal of the project derives from the recent proof of concept that mucosal vaccines are feasible in humans.
In this project, existing antigens, which are known to be protective in animal models against HIV and TB, will be formulated for mucosal delivery and tested in clinical trials. The antigens used for the initial clinical trials will be the latest generation of the envelope protein of HIV, which, being deleted of the loop 2, unmasks some of the conserved epitopes and induces broadly neutralising antibodies against primary isolates of HIV, the Gag and Tat proteins of HIV and the fusion protein of Ag85B and ESAT-6 of TB.
While the first trials are being performed, new systems to deliver mucosal vaccines and basic mechanisms of mucosal immune responses and memory in humans will be studied. This will allow better understanding of the clinical results and optimisation of second-generation vaccines to be tested in developing countries during the second phase of the project.
The project will be managed using the industrial knowledge of planning and management, to focus the participating laboratories in advancing the development of vaccines against HIV, TB and malaria while increasing the understanding of mucosal immunology.


HIV/AIDS and TB are causing a global health crisis unprecedented in the recent history of mankind and account for more than 4 million deaths every year, with the majority of this occurring in developing countries, particularly in sub-Saharan Africa. Since the start of the HIV epidemic, 21 million people have died and 57 million people have become infected. Mycobacterium tuberculosis affects one-third of the world population and represents the main cause of death in HIV-infected patients. Furthermore, TB represents a dramatic problem in Eastern Europe due to the extremely high prevalence of drug-resistant TB. This epidemiological situation is a major problem for all of Europe due to the impact of the migration of the spread of clinically relevant strains (World Health Organisation report 2002).

No vaccines have yet been developed for HIV and the efficacy of the currently used BCG vaccine varies in different populations and regions from 0 to 80%. Despite this, vaccination is one of the most cost-effective interventions; the economic value associated with vaccines, mainly those for developing countries, is negligible but industry finds them an unattractive area of investment.

The vast majority of existing vaccines are still administered by systemic injection. Although widely accepted, parenteral vaccination is not devoid of potential drawbacks. Most of the pathogens invade their human hosts at the level of the mucosal surfaces, which represent the very first antimicrobial barrier through non-specific (anatomical) and specific (immune) defence mechanisms. Mucosal vaccination would offer several advantages over the parenteral route of vaccination. Firstly, by inducing local microbial-specific immune responses, it would block pathogens at the port of entry, thus increasing the general efficacy of the vaccine. It is therefore likely that highly effective vaccines against mucosally transmitted diseases such as HIV/AIDS and TB, can effectively engage the mucosal immune system. Secondly, by avoiding the traumatic procedure of injection, mucosal vaccination would increase the compliance and consequently the coverage. Thirdly, it could facilitate vaccine delivery, especially in poorer countries. Last, but not least, mucosal immunisation would significantly decrease the risk of unwanted spread of infectious agents via contaminated syringes, especially in areas with a high incidence of viral hepatitis and human immunodeficiency virus infections.

It has been recently shown, both in mice and in humans, that the mucosal route is optimal for boosting immune responses primed by systemic immunisations (e.g. intramuscular). Considering that a great part of the population in developing countries is already vaccinated with BCG, it is expected that TB mucosal vaccines would be also more effective acting as a boost to systemic vaccination.

In consideration of the extremely high prevalence and incidence of HIV and TB infections, the development of effective mucosal vaccines would have a tremendous impact, forming the basis for a global use and subsequent impact on general public health, both in Europe and in developing countries.


The aim of the project is to develop vaccines that induce mucosal and systemic immunity against HIV/AIDS and TB. Existing antigens, which are known to be protective in animal models, will be formulated for mucosal delivery and tested in clinical trials. In parallel, pre-clinical studies will be performed to optimise mucosal vaccination against HIV, TB and malaria. Ultimately, the ambitious but realistic goal of the project is to provide candidate mucosal vaccines against HIV and TB that could subsequently enter the path towards licensure through phase II and III clinical trials in developing countries.

Expected results:

  1. Perform phase I clinical trials in Europe with the available mucosal antigens against HIV/AIDS and TB (two to three vaccine candidates).
  2. Develop second generation, effective vaccine candidates against HIV, TB and malaria.
  3. Select the most promising vaccine candidates by comparative testing in animal models of increasing relevance for humans (mice, guinea pigs [TB], monkeys).
  4. Perform phase I clinical trials in Africa with the vaccine candidates that have shown to be safe and immunogenic in clinical trials performed in Europe (up to two vaccine candidates).
  5. Perform phase I clinical trials in Europe with new vaccine candidates against TB and HIV developed by the consortium (up to three vaccine candidates).

On the whole, the MUVAPRED integrated project is aimed at achieving, within the five-year lifetime of the project, the clinical demonstration of safety and immunogenicity in healthy volunteers of vaccine candidates against HIV and TB infections, to be administered via mucosal routes and to advance the basic knowledge on the possible development of mucosal vaccines against malaria. The achievement of these results will provide safe and powerful mucosal vaccines to be advanced in efficacy trials in developing countries.

Potential applications:

This large consortium, including a major vaccine manufacturer and academic groups with expertise in clinical vaccine development, mucosal and systemic human immunity, animal models and vaccine delivery, will focus the skills of the individual participants towards the development of HIV, TB and malaria mucosal vaccines to be used in developing countries. The consortium will integrate different approaches and disciplines, and provide the necessary critical mass to test and compare different scientific ideas with the aim of delivering vaccines needed mainly in developing countries.


Rino Rappuoli
Chiron S.r.l.
Via Fiorentina, 1
53100 Siena


Official Address Other Information
2Gordon Dougan
Microbial Pathogenesis (team 15)
Wellcome Trust Sanger Institute
Wellcome Trust Genome Campus
UK-CB10 1SA Cambridge
United Kingdom
3Jan Holmgren

Göteborg University
Department of Medical Microbiology
and Immunology
P.O. Box 435SE
405 30 Göteborg

4Nils Lycke
Department of Clinical Immunology
Guldhedsgatan 10 SE
413 46 Göteborg
5Brigitte Gicquel
Institut Pasteur
Unité de Génétique Mycobacterienne
25 rue du Dr Roux
FR-75724 Paris
Cedex 15


6 Nathalie Winter
Institut Pasteur
Unité de Génétique Mycobacterienne
25 rue du Dr Roux
FR-75724 Paris
Cedex 15
7 Gianni Pozzi
Donata Medaglini
Università di Siena,
Dipartimento di Biologia Molecolare, LA.M.M.B.
Policlinico Le Scotte

V.le Bracci 16
IT-53100 Siena
8 Stefan H.E. Kaufmann
Max Planck Institute for Infection Biology,
Department of Immunology

Schumannstrasse 21/22
DE-10117 Berlin

9 Barbara Ensoli

Director AIDS Division
Department of Infectious,
Parasitic and Immune-Mediated Diseases
Istituto Superiore di Sanità
Viale Regina Elena 299
IT-00161 Rome

10Antonio Cassone
Director Department of Infectious,
Parasitic and Immune-Mediated Diseases
Viale Regina Elena 299IT0
0161 Rome

11 Antonio Lanzavecchia
Institute for Research in Biomedicine (IRB)

Via Vincenzo Vela, 6
CH-6500 Bellinzona

12 Paul Racz
Bernhard-Nocht-Institute for Tropical Medicine

Bernhard-Nocht-Str. 74
DE-20359 Hamburg

13 Thomas Lehner
Mucosal Immunology Group,
Guy’s King’s and St Thomas’ Medical
and Dental School

King’s College
UK-SE1 9RT London
United Kingdom

14 Kingston Mills
Immune Regulation Research Laboratory, Department of Biochemistry

Trinity College
IE-2 Dublin

15 Peter Andersen
Statens Serum Institute,
Department of Infectious
Disease Immunology

Artillerivej 5
DK-2300 Copenhagen S

16 Francesco Dieli
Consiglio nazionale delle Ricerche
Ist. Biomedicina e Immunologia Molecolare

Corso Tukory 211
IT-90134 Palermo
17 Alberto Mantovani
Mario Negri
Istituto di Ricerche Farmacologiche

Via Eritrea 62
IT-20157 Milan
18 Andreas Radbruch
German Arthritis Research Center

Scientific Director
Deutsches Rheuma-Forschungszentrum
Berlin (DRFZ)
19 David Lewis
St. George’s Hospital
Medical School
Vaccine Institute,
Department of Cellular and Molecular Medicine

Cranmer Terrace
UK-SW17 0RE London
United Kingdom

20 Peter SEBO
Academy of Sciences
of the Czech Republic
Institute of Microbiology

Videnska 1083
CZ-142 20 Prague 4
Czech Republic
21 Philip Marsh
Centre for Emergency Preparedness
and Response (CEPR),Health Protection Agency

Porton Down
UK-SP4 0JG Salisbury
United Kingdom

22 Gianfranco Del Prete
University of Florence
Dip. Medicina Interna

Viale Morgagni 85
IT-50134 Florence


23 Oumou Younoussa Sow

Service de Pneumo-Phtisiologie

BP 634 Conakry
Republic of Guinea

24 Giampietro Corradin
University of Lausanne
Institute of Biochemistry

CH-1066 Epalinges

25 Aldo Tagliabue
Alta Srl

Via Nino Bixio 15
IT-53100 Siena
26 Mahavir Singh
LIONEX Diagnostic and Therapeutics Gmbh

Mascheroder Weg 1 b
DE-38124 Braunschweig
27 Christoph Heinzen

Kirchstrasse 1
CH-5605 Dottikon
28Howard Engers
The Armauer Hansen Research Institute
Alert Campus
Jimma Road PO Box 1005
Addis Ababa
Tel: + 251 11 321 1334
Fax: + 251 11 321 1563
29Gita Ramjee
South African Research Council HIV
Prevention Unit (MRCHPU)
123 Jan Hofmeyer Road, Westville
PO Box 19070
Tel: + 031 242 3600
Fax: + 031 242 3806

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